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1.
Genome Res ; 34(6): 822-836, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39009472

RESUMEN

N 6-Methyladenosine (m6A) is a prevalent and highly regulated RNA modification essential for RNA metabolism and normal brain function. It is particularly important in the hippocampus, where m6A is implicated in neurogenesis and learning. Although extensively studied, its presence in specific cell types remains poorly understood. We investigated m6A in the hippocampus at a single-cell resolution, revealing a comprehensive landscape of m6A modifications within individual cells. Through our analysis, we uncovered transcripts exhibiting a dense m6A profile, notably linked to neurological disorders such as Alzheimer's disease. Our findings suggest a pivotal role of m6A-containing transcripts, particularly in the context of CAMK2A neurons. Overall, this work provides new insights into the molecular mechanisms underlying hippocampal physiology and lays the foundation for future studies investigating the dynamic nature of m6A RNA methylation in the healthy and diseased brain.


Asunto(s)
Adenosina , Hipocampo , Análisis de la Célula Individual , Hipocampo/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Animales , Análisis de la Célula Individual/métodos , Ratones , Neuronas/metabolismo , Procesamiento Postranscripcional del ARN , Metilación , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , ARN/metabolismo , ARN/genética , Humanos , Metilación de ARN
2.
Theranostics ; 14(9): 3548-3564, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38948068

RESUMEN

Over the past two decades, metronomic chemotherapy has gained considerable attention and has demonstrated remarkable success in the treatment of cancer. Through chronic administration and low-dose regimens, metronomic chemotherapy is associated with fewer adverse events but still effectively induces disease control. The identification of its antiangiogenic properties, direct impact on cancer cells, immunomodulatory effects on the tumour microenvironment, and metabolic reprogramming ability has established the intrinsic multitargeted nature of this therapeutic approach. Recently, the utilization of metronomic chemotherapy has evolved from salvage treatment for metastatic disease to adjuvant maintenance therapy for high-risk cancer patients, which has been prompted by the success of several substantial phase III trials. In this review, we delve into the mechanisms underlying the antitumour effects of metronomic chemotherapy and provide insights into potential combinations with other therapies for the treatment of various malignancies. Additionally, we discuss health-economic advantages and candidates for the utilization of this treatment option.


Asunto(s)
Administración Metronómica , Neoplasias , Microambiente Tumoral , Humanos , Neoplasias/tratamiento farmacológico , Microambiente Tumoral/efectos de los fármacos , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación
3.
Water Sci Technol ; 90(1): 287-302, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39007320

RESUMEN

Extracellular polymeric substances (EPS) are a critical influencing factor in sludge dewatering. Disrupting such EPS contributes to the release of bound water in sludge, enhancing the sludge dewatering performance. In This study, quaternized straw fibers that are destructive to the EPS structure and components in active sludge were prepared useing heterogeneous free radical graft polymerization. Straw fibers, dimethyl diallyl ammonium chloride (DMDAAC), ammonium persulfate (APS), and acrylamide (AM) were taken as the substrate, grafting monomer, catalyst, and cross-linking agent, respectively.The optimal processing conditions determined for the DMDAAC-based quaternization and graft modification of straw fibers were as follows: reaction temperature of 60 °C, reaction time of 5 h, 0.100 g of catalyst APS dosage per gram of straw, and 3.000 ml of DMDAAC dosage per gram of straw. The optimal processing conditions yielded 1.335 g of modified straw fibers per gram of straw, 33.67% grafting rate, and 31.70% substitution of the quaternary ammonium groups. The capillary suction time (CST) was conditioned from 243.3 ± 22.6 s in the original sludge to 134.5 ± 34.45 s. The specific resistance to filtration (SRF) was reduced from 8.82 ± 0.51 × 1012 m/kg in the original sludge to 4.59 ± 0.23 × 1012 m/kg.


Asunto(s)
Aguas del Alcantarillado , Aguas del Alcantarillado/química , Eliminación de Residuos Líquidos/métodos , Compuestos de Amonio Cuaternario/química , Compuestos Alílicos/química
4.
J Environ Manage ; 366: 121793, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38991342

RESUMEN

Acidic nitrification, as a novel process for treating wastewater without sufficient alkalinity, has received increasing attention over the years. In this study, a continuous-flow reactor with aerobic granular sludge was successful operated at low pH (<6.5) performing high-rate acidic nitrification. Volumetric ammonium oxidation rate of 0.4-1.2 kg/(m3·d) were achieved with the specific biomass activities of 5.8-13.9 mg N/(gVSS·h). Stable partial nitritation with nitrite accumulation efficiency over 85% could be maintained at pH above 6 with the aid of residual ammonium, whereas the nitrite accumulation disappeared when pH was below 6. Interestingly, the granule morphology significantly improved during the acidic operation. The increased secretion of extracellular polymeric substances (especially polysaccharides) suggested a self-protective behavior of microbes in the aerobic granules against acidic stress. 16S rRNA gene sequencing analyses indicated that Candidatus Nitrospira defluvii was always the dominant nitrite-oxidizing bacteria, while the dominant ammonia-oxidizing bacteria shifted from Nitrosomonas europaea to Nitrosomonas mobilis. This study, for the first time, demonstrated the improved stability of aerobic granules under acidic conditions, and also highlighted aerobic granules as a useful solution to achieve high-rate acidic nitrification.

5.
Am J Transl Res ; 16(6): 2212-2232, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006258

RESUMEN

BACKGROUND: Breast cancer is the most common malignancy in women, with its prognosis varying greatly according to its subtype. Triple-negative breast cancer (TNBC) has the worst prognosis among all subtypes. Glycosylation is a critical factor influencing the prognosis of patients with TNBC. Our aim is to develop a tumor prognosis model by analyzing genes related to glycosylation to predict patient outcomes. METHODS: The dataset used in this study was downloaded from the Cancer Genome Atlas Program (TCGA) database, and predictive genes were identified through Cox one-way regression analysis. The model genes with the highest risk scores among the 18 samples were obtained by lasso regression analysis to establish the model. We analyzed the pathways affecting the progression of TNBC and discovered key genes for subsequent research. RESULTS: Our model was constructed using data from TCGA database and validated through Kaplan-Meier curve analysis and Receiver Operating Characteristic (ROC) curve assessment. Our analysis revealed that a high expression of tumor-related chemokines in the high-risk group may be associated with poor tumor prognosis. Furthermore, we conducted a random survival forest analysis and identified two significant genes, namely DPM2 and PINK1, which have been selected for further investigation. CONCLUSION: The prognostic analysis model, developed based on the glycosylation genes in TNBC, exhibits excellent validation efficacy. This model is valuable for the prognostic analysis of patients with TNBC.

6.
Artículo en Inglés | MEDLINE | ID: mdl-39032127

RESUMEN

This study explored the effectiveness of a short-term mindfulness-based intervention (MBI) on psychological distress, mindfulness levels, emotion regulation, and impulsivity among college students with non-suicidal self-injury (NSSI). Participants completed four questionnaires, including the Five Facet Mindfulness Questionnaire, the Depression Anxiety Stress Scale, the Emotion Regulation Questionnaire, and the Brief Barratt Impulsivity Scale, and two behavioral tasks, including an emotion regulation task and a stop signal task (SST), at three time points. Compared with the healthy group, the NSSI group had a significantly greater level of psychological distress and a lower level of mindfulness. Compared with the NSSI control group and the healthy group, the NSSI MBI group had significantly increased mindfulness levels and decreased psychological distress after the intervention. In the NSSI MBI group, regardless of which emotion regulation strategy was adopted when viewing negative pictures, the intensity of negative emotions during the emotion regulation task was significantly reduced. Moreover, in the NSSI MBI group, the effectiveness of the MBI on the mindfulness level, stress level, and emotion regulation process was maintained at the follow-up. The present study provided empirical support that short-term MBI has the potential to help individuals with NSSI by enhancing their emotion regulation.

7.
Glia ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39041109

RESUMEN

Neuroinflammation plays important roles in retinal ganglion cell (RGC) degeneration in glaucoma. MicroRNA-146 (miR-146) has been shown to regulate inflammatory response in neurodegenerative diseases. In this study, whether and how miR-146 could affect RGC injury in chronic ocular hypertension (COH) experimental glaucoma were investigated. We showed that in the members of miR-146 family only miR-146a-5p expression was upregulated in COH retinas. The upregulation of miR-146a-5p was observed in the activated microglia and Müller cells both in primary cultured conditions and in COH retinas, but mainly occurred in microglia. Overexpression of miR-146a-5p in COH retinas reduced the levels pro-inflammatory cytokines and upregulated the levels of anti-inflammatory cytokines, which were further confirmed in the activated primary cultured microglia. Transfection of miR-146a-5p mimic increased the percentage of anti-inflammatory phenotype in the activated BV2 microglia, while transfection of miR-146a-5p inhibitor resulted in the opposite effects. Transfection of miR-146a-5p mimic/agomir inhibited the levels of interleukin-1 receptor associated kinase (IRAK1) and TNF receptor associated factor 6 (TRAF6) and phosphorylated NF-κB subunit p65. Dual luciferase reporter gene assay confirmed that miR-146a-5p could directly target IRAK1 and TRAF6. Moreover, downregulation of IRAK1 and TRAF6 by siRNA techniques or blocking NF-κB by SN50 in cultured microglia reversed the miR-146a-5p inhibitor-induced changes of inflammatory cytokines. In COH retinas, overexpression of miR-146a-5p reduced RGC apoptosis, increased RGC survival, and partially rescued the amplitudes of photopic negative response. Our results demonstrate that overexpression of miR-146a-5p attenuates RGC injury in glaucoma by reducing neuroinflammation through downregulating IRAK1/TRAF6/NF-κB signaling pathway in microglia.

8.
Front Pediatr ; 12: 1331089, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38978837

RESUMEN

Purpose: The aim of this study was to evaluate the surgical outcomes of proximal femoral bone cysts in pediatric patients. Methods: We retrospectively analyzed 41 pediatric patients (31 males and 10 females, mean age 7.47 ± 2.67 years, range 2.03-14.67 years) diagnosed with proximal femoral bone cysts treated at a single institute between March 2009 and November 2021. Data included demographics, preoperative details, intraoperative conditions, surgical techniques, postoperative outcomes, recurrence, and complications. Results: Of the participants, 68% presented with simple bone cysts and 32% with aneurysmal bone cysts. Prior to surgery, 32% exhibited pathological fractures. Surgical methods included lesion curettage, defect filling using allograft bone and Minimally-Invasive Injectable Graft ×3, and varied fixation techniques. Postoperative recurrence (17%) was associated with cyst location between the capital femoral epiphysis and the linea intertrochanterica (P = 0.010). At the final assessment (mean follow-up: 26.51 ± 18.99 months), all showed radiological bony union with 93% rated as "good" and 7% as 'fair' based on Ratliff hip scores. Complications arose in 20% of patients, significantly correlated with prior pathological fractures (P = 0.007) and their association with the linea intertrochanterica (P = 0.004). Those with fractures reported higher intraoperative blood loss (P = 0.015) and longer surgery durations (P = 0.012) compared to those without. Conclusion: Treating pediatric proximal femoral bone cysts using techniques such as lesion curettage, defect filling, and selective internal fixation yields favorable outcomes. The presence of pathological fractures can prolong surgical time, increase intraoperative blood loss, and elevate postoperative complication risks. Hence, early surgical intervention for these cysts is recommended to prevent fractures.

9.
J Agric Food Chem ; 72(28): 15704-15714, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38976778

RESUMEN

Pueraria lobata (Willd.) Ohwi, known as kudzu and used as a "longevity powder" in China, is an edible plant which is rich in flavonoids and believed to be useful for regulating blood sugar and treating diabetes, although the modes of action are unknown. Here, a total of 53 flavonoids including 6 novel compounds were isolated from kudzu using multidimensional preparative liquid chromatography. The flavonoid components were found to lower blood sugar levels, promote urine sugar levels in mice, and reduce the urine volume. Molecular docking and in vitro assays suggested that the antidiabetic effect of kudzu was attributed to at least three targets: sodium-dependent glucose transporter 2 (SGLT2), protein tyrosine phosphatase-1B (PTP1B), and alpha-glucosidase (AG). This study suggests a possible mechanism for the antidiabetic effect that may involve the synergistic action of multiple active compounds from kudzu.


Asunto(s)
Flavonoides , Hipoglucemiantes , Extractos Vegetales , Proteína Tirosina Fosfatasa no Receptora Tipo 1 , Pueraria , Pueraria/química , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Flavonoides/química , Animales , Ratones , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Humanos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Simulación del Acoplamiento Molecular , Masculino , alfa-Glucosidasas/metabolismo , alfa-Glucosidasas/química , Glucemia/metabolismo , Plantas Comestibles/química
10.
Front Public Health ; 12: 1419665, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39026590

RESUMEN

Aims: This study aims to assess the status and related factors among healthcare workers (HCWs) in designated quarantine-hospital-site (DQHS) based on the model of health ecology. Methods: The cross-sectional study was conducted from April to May, 2022, which included 351 valid samples. We measured sleep quality using the Pittsburgh Sleep Quality Index, which encompasses seven dimensions: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction. Each dimension is scored individually, contributing to an overall sleep quality score. Factors associated with the sleep quality of HCWs in DQHS were divided into individual, behavioral, interpersonal and social dimensions. Hierarchical linear regressions were conducted to identify the potential factors associated with sleep quality among HCWs in DQHS. Results: HCWs in DQHS had a statistically higher sleep quality than the Chinese national norm. HCWs who were female, afraid of Coronavirus disease, had more negative emotions, frequently worked overtime, were married, and had a higher income were more likely to experience worse sleep quality (p < 0.05), while those who worked between 51 and 70 h weekly, treated over 10 patients daily, and engaged in more health behaviors may have better sleep quality (p < 0.05). Conclusion: This study revealed a worrying level of sleep quality among HCWs in DQHS. The government, hospital managers, and families should collaborate to ensure the sleep quality of HCWs in DQHS.


Asunto(s)
COVID-19 , Personal de Salud , Cuarentena , Calidad del Sueño , Humanos , Estudios Transversales , Masculino , Femenino , China/epidemiología , COVID-19/epidemiología , Cuarentena/psicología , Adulto , Personal de Salud/estadística & datos numéricos , Personal de Salud/psicología , Persona de Mediana Edad , Encuestas y Cuestionarios , Trastornos del Sueño-Vigilia/epidemiología , Hospitales/estadística & datos numéricos , Pandemias
11.
Front Oncol ; 14: 1420917, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39040454

RESUMEN

Background: There remains a pressing need to identify biomarkers capable of reliably predicting prognostic outcomes for colorectal cancer (CRC) patients. As several body composition parameters have recently been reported to exhibit varying levels of prognostic significance in particular cancers, the present study was devised to assess the ability of body composition to predict long-term outcomes for CRC patients with different stages of disease. Methods: In total, this retrospective analysis enrolled 327 stage I-III CRC patients whose medical records were accessed for baseline demographic and clinical data. Primary outcomes for these patients included disease-free and overall survival (DFS and OS). The prognostic performance of different musculature, visceral, and subcutaneous fat measurements from preoperative computed tomography (CT) scans was assessed. Results: Over the course of follow-up, 93 of the enrolled patients experienced recurrent disease and 39 died. Through multivariate Cox regression analyses, the visceral/subcutaneous fat area (V/S) ratio was found to be independently associated with patient DFS (HR=1.93, 95% CI: 1.24-3.01, P=0.004), and the skeletal muscle index (SMI) as an independent predictor for OS (HR=0.43, 95% CI: 0.21-0.89, P=0.023). Through subgroup analyses, higher V/S ratios were found to be correlated with reduced DFS among patients with stage T3/4 (P=0.011), lymph node metastasis-positive (P=0.002), and TNM stage III (P=0.002) disease, whereas a higher SMI was associated with better OS in all T stages (P=0.034, P=0.015), lymph node metastasis-positive cases (P=0.020), and in patients with TNM stage III disease (P=0.020). Conclusion: Both the V/S ratio and SMI offer potential utility as clinical biomarkers associated with long-term CRC patient prognosis. A higher V/S ratio and a lower SMI are closely related to poorer outcomes in patients with more advanced disease.

12.
Cereb Cortex ; 34(6)2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38889442

RESUMEN

Neurofeedback, a non-invasive intervention, has been increasingly used as a potential treatment for major depressive disorders. However, the effectiveness of neurofeedback in alleviating depressive symptoms remains uncertain. To address this gap, we conducted a comprehensive meta-analysis to evaluate the efficacy of neurofeedback as a treatment for major depressive disorders. We conducted a comprehensive meta-analysis of 22 studies investigating the effects of neurofeedback interventions on depression symptoms, neurophysiological outcomes, and neuropsychological function. Our analysis included the calculation of Hedges' g effect sizes and explored various moderators like intervention settings, study designs, and demographics. Our findings revealed that neurofeedback intervention had a significant impact on depression symptoms (Hedges' g = -0.600) and neurophysiological outcomes (Hedges' g = -0.726). We also observed a moderate effect size for neurofeedback intervention on neuropsychological function (Hedges' g = -0.418). As expected, we observed that longer intervention length was associated with better outcomes for depressive symptoms (ß = -4.36, P < 0.001) and neuropsychological function (ß = -2.89, P = 0.003). Surprisingly, we found that shorter neurofeedback sessions were associated with improvements in neurophysiological outcomes (ß = 3.34, P < 0.001). Our meta-analysis provides compelling evidence that neurofeedback holds promising potential as a non-pharmacological intervention option for effectively improving depressive symptoms, neurophysiological outcomes, and neuropsychological function in individuals with major depressive disorders.


Asunto(s)
Trastorno Depresivo Mayor , Neurorretroalimentación , Neurorretroalimentación/métodos , Humanos , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Mayor/fisiopatología , Resultado del Tratamiento , Electroencefalografía/métodos
13.
Langmuir ; 40(27): 14027-14036, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38920353

RESUMEN

The accurate measurement of pH in highly alkaline environments is critical for various industrial applications but remains a complex task. This paper discusses the development of novel Fe-doped SrCoOx-based FET sensors for the detection of extreme alkaline pH levels. Through a comprehensive investigation of the effects of Fe doping on the structure, electrical properties, and sensing performance of SrCoOx, we have identified the optimal doping level that significantly enhances the sensor's performance in highly alkaline conditions. With a Fe doping level of 5 mol %, the sensitivity of the sensor improves to 0.86 lg(Ω)/pH while maintaining the response rate. Further increasing the Fe doping to 10 mol % results in a sensor that demonstrates favorable response time, a suitable pH range, and a linear correlation between lg(R) and pH. The combination of X-ray photoelectron spectroscopy and X-ray diffraction analysis provides insight into the regulation mechanisms of Fe doping on the crystal structure, electronic structure, and oxygen vacancy concentration of SrCoOx. Our findings indicate that Fe doping leads to an increase in oxygen vacancy concentration and a decrease in the energy barrier for oxygen ion migration, which contributes to the improved sensing performance of the Fe-doped SrCoOx sensors. Additionally, the study highlights the influence of oxygen vacancy concentration on the electrical properties of SrCoOx. Precise control over the concentration of oxygen vacancies is crucial for optimizing the sensitivity and response speed of SrCoOx FET sensors under extreme alkalinity conditions.

14.
J Pharm Biomed Anal ; 248: 116289, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38901158

RESUMEN

Traditional Chinese medicines (TCMs) are popular in clinic because of their safety and efficacy. They contain abundant natural active compounds, which are important sources of new drug discovery. However, how to efficiently identify active compounds from complex ingredients remains a challenge. In this study, a method combining UHPLC-MS/MS characterization and in silico screening was developed to discover compounds with dopamine D2 receptor (D2R) activity in Stephania epigaea (S. epigaea). By combining the compounds identified in S. epigaea by UHPLC-MS/MS with reported compounds, a virtual library of 80 compounds was constructed for in silico screening. Potentially active compounds were chosen based on screening scores and subsequently tested for in vitro activity on a transfected cell line CHO-K1-D2 model using label-free cellular phenotypic assay. Three D2R agonists and five D2R antagonists were identified. (-)-Asimilobine, N-nornuciferine and (-)-roemerine were reported for the first time as D2R agonists, with EC50 values of 0.35 ± 0.04 µM, 1.37 ± 0.10 µM and 0.82 ± 0.22 µM, respectively. Their target specificity was validated by desensitization and antagonism assay. (-)-Isocorypalmine, (-)-tetrahydropalmatine, (-)-discretine, (+)-corydaline and (-)-roemeroline showed strong antagonistic activity on D2R with IC50 values of 92 ± 9.9 nM, 1.73 ± 0.13 µM, 0.34 ± 0.02 µM, 2.09 ± 0.22 µM and 0.85 ± 0.08 µM, respectively. Their kinetic binding profiles were characterized using co-stimulation assay and they were both D2R competitive antagonists. We docked these ligands with human D2R crystal structure and analyzed the structure-activity relationship of aporphine-type D2R agonists and protoberberine-type D2R antagonists. These results would help to elucidate the mechanism of action of S. epigaea for its analgesic and sedative efficacy and benefit for D2R drug design. This study demonstrated the potential of integrating UHPLC-MS/MS with in silico and in vitro screening for accelerating the discovery of active compounds from TCMs.


Asunto(s)
Cricetulus , Receptores de Dopamina D2 , Stephania , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Células CHO , Animales , Cromatografía Líquida de Alta Presión/métodos , Stephania/química , Receptores de Dopamina D2/metabolismo , Simulación por Computador , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Antagonistas de los Receptores de Dopamina D2/farmacología , Antagonistas de los Receptores de Dopamina D2/química , Descubrimiento de Drogas/métodos , Agonistas de Dopamina/farmacología , Agonistas de Dopamina/química , Humanos , Medicina Tradicional China/métodos , Cromatografía Líquida con Espectrometría de Masas
15.
Virulence ; 15(1): 2368080, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38899573

RESUMEN

Dendritic cells (DCs) present an ideal target for delivering immunogenic cargo due to their potent antigen-presenting capabilities. This targeting approach holds promise in vaccine development by enhancing the efficiency of antigen recognition and capture by DCs. To identify a high-affinity targeting peptide binding to rabbit DCs, rabbit monocyte-derived DCs (raMoDCs) were isolated and cultured, and a novel peptide, HS (HSLRHDYGYPGH), was identified using a phage-displayed peptide library. Alongside HS, two other DC-targeting peptides, KC1 and MY, previously validated in our laboratory, were employed to construct recombinant Lactgobacillus reuteri fusion-expressed rabbit hemorrhagic disease virus (RHDV) capsid protein VP60. These recombinant Lactobacillus strains were named HS-VP60/L. reuteri, KC1-VP60/L. reuteri, and MY-VP60/L. reuteri. The ability of these recombinant Lactobacillus to bind rabbit DCs was evaluated both in vivo and in vitro. Results demonstrated that the DC-targeting peptide KC1 significantly enhanced the capture efficiency of recombinant Lactobacillus by raMoDCs, promoted DC maturation, and increased cytokine secretion. Furthermore, oral administration of KC1-VP60/L. reuteri effectively induced SIgA and IgG production in rabbits, prolonged rabbit survival post-challenge, and reduced RHDV copies in organs. In summary, the DC-targeting peptide KC1 exhibited robust binding to raMoDCs, and recombinant Lactobacillus expressing KC1-VP60 protein antigens efficiently induced systemic and mucosal immune responses in rabbits, conferring protective efficacy against RHDV. This study offers valuable insights for the development of novel RHDV vaccines.


Asunto(s)
Células Dendríticas , Virus de la Enfermedad Hemorrágica del Conejo , Limosilactobacillus reuteri , Péptidos , Animales , Células Dendríticas/inmunología , Conejos , Virus de la Enfermedad Hemorrágica del Conejo/inmunología , Virus de la Enfermedad Hemorrágica del Conejo/genética , Limosilactobacillus reuteri/genética , Limosilactobacillus reuteri/inmunología , Péptidos/inmunología , Péptidos/genética , Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/inmunología , Infecciones por Reoviridae/prevención & control , Infecciones por Reoviridae/inmunología , Proteínas de la Cápside/genética , Proteínas de la Cápside/inmunología , Vacunas Virales/inmunología , Vacunas Virales/genética , Lactobacillus/genética , Lactobacillus/inmunología
16.
Front Immunol ; 15: 1401972, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38911858

RESUMEN

Myasthenia gravis with positive MuSK antibody often involves the bulbar muscles and is usually refractory to acetylcholinesterase inhibitors. For MuSK-MG patients who experience acute exacerbations and do not respond to conventional treatments, there is an urgent need to find more suitable treatment options. With the advent of biologic agents, efgartigimod has shown promising results in the treatment of MG. We report a 65-year-old MuSK-MG patient who presented with impaired eye movements initially, and the symptoms rapidly worsened within a week, affecting the limbs and neck muscles, and had difficulties in chewing and swallowing. Lymphoplasmapheresis did not achieve satisfactory results, but after a cycle of efgartigimod treatment, the patient's symptoms gradually improved and remained in a good clinical state for several months.


Asunto(s)
Miastenia Gravis , Receptores Colinérgicos , Humanos , Miastenia Gravis/tratamiento farmacológico , Anciano , Receptores Colinérgicos/inmunología , Resultado del Tratamiento , Proteínas Tirosina Quinasas Receptoras/inmunología , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Masculino , Femenino
17.
Pathogens ; 13(5)2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38787256

RESUMEN

Tibetan pig is a unique pig breed native to the Qinghai-Tibet Plateau. To investigate viral communities associated with porcine respiratory disease complex (PRDC), 167 respiratory samples were collected from Tibetan pigs in the Ganzi Tibetan autonomous prefecture of Sichuan province. Following library construction and Illunima Novaseq sequencing, 18 distinct viruses belonging to 15 viral taxonomic families were identified in Tibetan pigs with PRDC. Among the 18 detected viruses, 3 viruses were associated with PRDC, including porcine circovirus type 2 (PCV-2), Torque teno sus virus (TTSuV), and porcine cytomegalovirus (PCMV). The genomic sequences of two PCV-2 strains, three TTSuV strains, and one novel Porprismacovirus strain were assembled by SOAPdenovo software (v2). Sequence alignment and phylogenetic analysis showed that both PCV-2 strains belonged to PCV-2d, three TTSuVs were classified to TTSuV2a and TTSuV2b genotypes, and the Porprismacovirus strain PPMV-SCgz-2022 showed a close genetic relationship with a virus of human origin. Recombination analysis indicated that PPMV-SCgz-2022 may have originated from recombination events between Human 16,806 × 66-213 strain and Porcine 17,668 × 82-593 strain. Furthermore, the high proportion of single infection or co-infection of PCV2/TTSuV2 provides insight into PRDC infection in Tibetan pigs. This is the first report of the viral communities in PRDC-affected Tibetan pigs in this region, and the results provides reference for the prevention and control of respiratory diseases in these animals.

19.
J Youth Adolesc ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740644

RESUMEN

Past research supports the detrimental effects of parental psychological control on adolescent school adjustment in both emotional and academic domains. However, how psychological control changes during adolescence, and how such developmental course is related to adolescent psychological well-being and academic functioning are unclear. The direction of effects between parenting and child behaviors is also inconclusive. This 3-year longitudinal study addressed these research gaps by using five waves of survey data on 710 Chinese adolescents of high school ages (Mean age at T1 = 15.54 years, SD = 0.45, 50% males). Using latent growth curve models and latent class growth analysis, the majority of adolescents (about 63%) reported gradual increases of parental psychological control in the first 2 years of high school but a slight decline afterwards, while the other 37% perceived low and stable levels. Results from parallel latent growth modeling suggested that trajectories of psychological control were positively related to developmental trends of internalizing problems (i.e., depression and anxiety) and maladaptive academic functioning, but negatively associated with the trajectory of adaptive academic functioning, as indexed by intercept-intercept and slope-slope associations. The random-intercept cross-lagged models further revealed that psychological control was predictive of adolescent anxiety and lower adaptive academic functioning, and bidirectionally associated with maladaptive academic-related beliefs and behaviors at the within-person level. Taken together, these findings highlight the crucial role of parental psychological control on adolescent school adjustment in the Chinese cultural context and support the reciprocal model of parent-child interactions.

20.
Sci Rep ; 14(1): 11455, 2024 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769329

RESUMEN

Cone-beam computed tomography (CBCT) is a crucial component of adaptive radiation therapy; however, it frequently encounters challenges such as artifacts and noise, significantly constraining its clinical utility. While CycleGAN is a widely employed method for CT image synthesis, it has notable limitations regarding the inadequate capture of global features. To tackle these challenges, we introduce a refined unsupervised learning model called improved vision transformer CycleGAN (IViT-CycleGAN). Firstly, we integrate a U-net framework that builds upon ViT. Next, we augment the feed-forward neural network by incorporating deep convolutional networks. Lastly, we enhance the stability of the model training process by introducing gradient penalty and integrating an additional loss term into the generator loss. The experiment demonstrates from multiple perspectives that our model-generated synthesizing CT(sCT) has significant advantages compared to other unsupervised learning models, thereby validating the clinical applicability and robustness of our model. In future clinical practice, our model has the potential to assist clinical practitioners in formulating precise radiotherapy plans.


Asunto(s)
Tomografía Computarizada de Haz Cónico , Redes Neurales de la Computación , Humanos , Tomografía Computarizada de Haz Cónico/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Algoritmos , Aprendizaje Automático no Supervisado
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